MR imaging of the human body can display both normal anatomy and a variety of organ pathologies, including tumors. For example, the liver, pancrease, spleen and gall bladder can be imaged by tomographic slides in various planes. The techniques used for MRI liver examination have included delineation by spin-echo, inversion recovery, and saturation recovery pulse sequences but definition of normal from abnormal has not been predictable. In hepatic MRI, specifically, contrast resolution of the hepatic images varies greatly depending on the data acquisition technique employed to obtain the image, although tumors associated with the liver or spleen usually result in prolongation of both the longitudinal (T.sub.l) and the transverse (T.sub. 2) relaxation times as compared with normal tissues. Earlier reports have emphasized the importance of using paramagnetic agents to increase the T.sub.l differences between normal and pathologic tissues and considered coincidental T.sub.2 diminution an impediment.
Paramagnetic contrast agents as free metal ions, chelates, or insoluble metal compounds have been described for use in enhancing intrinsic contrast in MR imaging. Such paramagnetic metals include gadolinium, chromium, copper, manganese, and iron. Because of possible toxicity, soluble chelates have been suggested for parenteral administration and insolubilized compounds for oral administration. Heretofore, however, the targeting of stable contrast agents to the liver and spleen has not been satisfactory.
An effective, safe reticuloendothelial system (RES) MRI contrast agent which can increase the sensitivity and differentiation of normal and pathologic tissue in the liver or spleen has not been previously described. This problem is aggravated by the fact that existing modalities for other imaging procedures for the liver and spleen have approximately a 10-20% false-negative rate for detecting hepatic metastases, and a 40-50% false-negative rate for detecting lymphomatous involvement, necessitating laproscopic staging. Further, as pointed out above, tumor involvement of liver, spleen and other tissues has consistently been shown to increase T.sub.1 and T.sub.2 relaxation parameters to a variable and unpredictable degree, which also results in a high incidence of false negatives. RES agents are useful because liver replaced by tumor does not possess RES cells and therefore does not take up the contrast agent. Non-RES agents more randomly distribute between normal and pathologic tissue.
Hepatic disease conditions resulting in abnormally high levels of iron in the liver have been shown to produce alterations of tissue relaxation times as observed by MRI. See, for example, Doyle, et al., Am. J. Roentgenol. (1982) 138: 193-200; Stark, et al., Radiology (1983) 148: 743 -751; and Runge, et al., Am. J. Roentgenol. (1983) 141: 943 -948. Observed decreases in T.sub.l have been attributed either to paramagnetic enhancement of longitudinal relaxation, or to alterations of hydrated tissue proteins. Heretofore, the production of T.sub.2 dimunition as seen in these disease states has not been produced with a potent, safe contrast agent. Soluble iron compounds have been tested as MRI contrast agents. Wesbey, et al., Radiology (1983) 149: 175 -180.